As many of the traditional mood stabilizers used to treat bipolar disorder, including lithium and valproic acid, carry some teratogenic risk and the reproductive safety of other medications, including the atypical antipsychotic agents, has not been well-characterized, many women with bipolar disorder decide to discontinue their treatment during pregnancy. A new study from Dr. Adele Viguera and her colleagues at the Massachusetts General Hospital and the Emory University School of Medicine helps to better define the risks associated with discontinuing treatment during pregnancy.

The study followed 89 women with bipolar disorder (69% type I, 31% type II) prospectively across pregnancy. Pregnant women (prior to 24 weeks gestation) were eligible for the study if they 1) were euthymic for at least 1 month prior to conception, 2) were receiving treatment with a mood stabilizer, or 3) had discontinued pharmacotherapy no more than 6 months prior to pregnancy or within the first trimester. Most subjects (>70%) were taking more than one psychotropic medication, typically a mood stabilizer in combination with an antidepressant and/or antipsychotic agent. This was a naturalistic study, and based on the recommendations of their own treaters, women elected either to maintain (n=62) or to discontinue (n=27) treatment with a mood stabilizer.

During the course of pregnancy, 70.8% of the participants experienced at least one mood episode. Most of these episodes were either depressive or mixed (74%), and 47% occurred during the first trimester. The risk of recurrence was significantly higher in women who discontinued treatment with mood stabilizers (85.5%) than those who maintained treatment (37.0%). In addition, the women who discontinued mood stabilizer spent over 40% of their pregnancy in an illness episode, versus only 8.8% among subjects who maintained treatment with a mood stabilizer.
The investigators also examined whether certain demographic or clinical variables were associated with increased risk of recurrence during pregnancy. The only pregnancy-related predictor of relapse was unplanned pregnancy. Clinical variables associated with a higher risk of recurrence included younger age at illness onset (RR=1.6), bipolar II disorder diagnosis (RR=1.5), history of rapid cycling (RR=1.5), history of mixed episodes (RR=1.5) and shorter duration of clinical stability since last episode (RR=1.5). Treatment factors associated with increased relapse rates included polytherapy with more than two psychotropic agents (RR=2.3), use of antidepressants (RR=2.0), primary mood stabilizer other than lithium (RR=1.6), and abrupt discontinuation (less than two weeks) of mood stabilizer (RR=1.4).

While this study has some limitations, it is the largest prospective study of the course of bipolar disorder during pregnancy to date and yields important data which can help to inform the treatment of bipolar illness during pregnancy. The study indicates that the risk of recurrent illness during pregnancy is extremely high, particularly when medications were discontinued. While the authors acknowledge that these findings may not generalize to other clinical populations as the study was conducted with subjects seen in a specialty research program, the findings clearly indicate that women with more severe or recurrent illness are at greatest risk for recurrent illness.

Consistent with a similar prospective study carried out in women with unipolar depression (Cohen et al, 2006), this study demonstrates that discontinuation of ongoing maintenance treatment in women with bipolar disorder carries a very high risk of recurrent illness. In short, pregnancy does not appear to be protective against psychiatric illness. Although there may be concerns regarding the use of psychotropic medications during pregnancy, these findings challenge the common practice of abruptly discontinuing maintenance treatment for bipolar disorder during pregnancy.

Ruta Nonacs, MD PhD

Viguera AC, Whitfield T, Baldessarini RJ, Newport DJ, et al. Risk of Recurrence in Women With Bipolar Disorder During Pregnancy: Prospective Study of Mood Stabilizer Discontinuation. Am J Psychiatry 2007; 164:1817-1824.

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Comments from Dr. Marlene Freeman

Medscape Interview With Dr. Adele Viguera

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